Differential Sensitivity of Germline and Somatic BRCA Variants to PARP Inhibitor in High-Grade Serous Ovarian Cancer
Abstract
:1. Introduction
2. Results
2.1. Patient Cohort and Alteration Descriptions
2.2. Clinicopathological Characteristics of the Patients with a Pathogenic Variant
2.3. Clinical Outcome of Patients According to the Presence of Germline or Somatic Pathogenic Alterations
3. Discussion
4. Material and Methods
4.1. Patients and Samples Collection
4.2. DNA Extraction and Qualification
4.3. BRCA1 and BRCA2 Variants Analysis
4.4. Bioinformatics and Data Analysis
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patients (n = 104) | ||
---|---|---|
Age at diagnosis | ||
Median (range) | 63.4 (30.4–87.0) | |
<60 | 41 | |
≥60 | 63 | |
FIGO Stage | ||
I | 6 | |
II | 3 | |
III | 36 | |
IV | 19 | |
Unknown | 40 | |
Type of specimen | ||
Biopsy | 28 | |
Surgical specimen | 70 | |
Unknown | 6 | |
Tumor cell content | ||
<50% | 16 | |
≥50% | 85 | |
Unknown | 3 | |
Clinical follow-up | ||
Yes | 91 | |
No | 13 | |
PARP inhibitor administration | ||
Yes | 58 | |
No | 33 | |
Unknown | 13 | |
Germline status | ||
Known | 80 | |
Unknown | 24 | |
Mutation present | ||
At the germline level | 47 | |
At the somatic level only | 33 | |
Genetic result not available | 24 | |
Gene mutated | ||
BRCA1 | 69 | |
BRCA2 | 35 |
Number of Samples | Univariate Analysis | ||||
---|---|---|---|---|---|
HR | 95% CI | p a | |||
PFS to first-line platinum-based chemotherapy | |||||
Gene affected (BRCA1; BRCA2) | 66 | 1.30 | 0.74–2.27 | 0.38 | |
BRCA genetic status (germline; somatic) | 66 | 1.09 | 0.63–1.91 | 0.77 | |
PFS to second-line PARP inhibitor treatment | |||||
Gene affected (BRCA1; BRCA2) | 49 | 1.17 | 0.32–4.24 | 0.80 | |
BRCA genetic status (germline; somatic) | 49 | 3.42 | 1.01–11.63 | 0.049 | |
OS | |||||
Gene affected (BRCA1; BRCA2) | 66 | 1.51 | 0.43–5.39 | 0.52 | |
BRCA genetic status (germline; somatic) | 66 | 2.40 | 0.68–8.48 | 0.17 |
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Vendrell, J.A.; Ban, I.O.; Solassol, I.; Audran, P.; Cabello-Aguilar, S.; Topart, D.; Lindet-Bourgeois, C.; Colombo, P.-E.; Legouffe, E.; D’Hondt, V.; et al. Differential Sensitivity of Germline and Somatic BRCA Variants to PARP Inhibitor in High-Grade Serous Ovarian Cancer. Int. J. Mol. Sci. 2023, 24, 14181. https://doi.org/10.3390/ijms241814181
Vendrell JA, Ban IO, Solassol I, Audran P, Cabello-Aguilar S, Topart D, Lindet-Bourgeois C, Colombo P-E, Legouffe E, D’Hondt V, et al. Differential Sensitivity of Germline and Somatic BRCA Variants to PARP Inhibitor in High-Grade Serous Ovarian Cancer. International Journal of Molecular Sciences. 2023; 24(18):14181. https://doi.org/10.3390/ijms241814181
Chicago/Turabian StyleVendrell, Julie A., Iulian O. Ban, Isabelle Solassol, Patricia Audran, Simon Cabello-Aguilar, Delphine Topart, Clothilde Lindet-Bourgeois, Pierre-Emmanuel Colombo, Eric Legouffe, Véronique D’Hondt, and et al. 2023. "Differential Sensitivity of Germline and Somatic BRCA Variants to PARP Inhibitor in High-Grade Serous Ovarian Cancer" International Journal of Molecular Sciences 24, no. 18: 14181. https://doi.org/10.3390/ijms241814181